This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase I study of bortezomib and temozolomide in subjects with a recurrent primary brain tumor (including primary CNS lymphoma) or recurrent brain metastases or confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective. The objectives of this study are: 1.1 To determine the dose-limiting toxicities (DLTs) and maximum tolerated doses (MTDs) for the combination of bortezomib and temozolomide in patients with recurrent high-grade gliomas, recurrent metastatic brain tumors or other refractory solid tumors. 1.2 To evaluate the pharmacokinetics of bortezomib in patients taking hepatic enzyme-inducing anticonvulsants (Group A) and in those who are not (Group B). 1.3 To assess whether bortezomib crosses into the central nervous system by measuring drug levels in the cerebrospinal fluid. 1.4 To describe the proportion of study patients treated with bortezomib and temozolomide who obtain a confirmed complete response or partial response.